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Management of Bladder Cancer Following Solid Organ Transplantation

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Management of Bladder Cancer Following Solid Organ Transplantation Hindawi Publishing Corporation Advances in Urology Volume 2011, Article ID 256985, 7 pages doi:10.1155/2011/256985 Clinical Study Management of Bladder Cancer following Solid Organ Transplantation Jeffrey J. Tomaszewski, Jeffrey A. Larson, Marc C. Smaldone, Matthew H. Hayn, and Stephen V. Jackman Department of Urology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA Correspondence should be addressed to Jeffrey J. Tomaszewski, [email protected] Received 16 July 2010; Revised 8 February 2011; Accepted 21 February 2011 Academic Editor: A. Stenzl Copyright © 2011 Jeffrey J. Tomaszewski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC) following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2%) following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients. 1. Introduction database to identify patients diagnosed with bladder urothe- lial carcinoma (BUC) following renal and liver transplan- Renal and liver transplantation are the optimal treatments tation between January 1992 and December 2007. We for end-stage renal and liver disease [1, 2]. While the devel- examined demographic information including gender, age opment of bladder cancer following renal and liver trans- at transplant and cancer diagnosis, type of immunosuppres- plantation is quite rare [3], transplant recipients have an sion, smoking history, and time to cancer diagnosis. Tumor increased incidence of bladder cancer [4, 5], ranging from characteristics, including clinical and pathologic stage, mode 0.08% to 2.1% [6, 7], and frequently present with higher- of presentation, treatment (including adjuvant therapy and stage bladder cancer compared to the general population urinary tract reconstruction), and tumor progression were [5]. Optimal management of bladder cancer among renal also evaluated. Postoperative outcomes reviewed include and liver transplant recipients is not well defined. Most disease recurrence, allograft function following treatment, management strategies have only been briefly described in overall and cancer-specific survival, and length of followup. anecdotal case reports [8]andretrospectiveseries[7]. We present our single institution experience managing bladder No patient had a history of bladder cancer or hematuria cancer after renal and liver transplantation. prior to transplantation. Transurethral resection of bladder tumor (TURBT) with or without intravesical immunother- 2. Patients and Methods apy or chemotherapy (one patient received mitomycin-C) was used for treating nonmuscle-invasive tumors. Patients Through an Institutional Review Board approved protocol, were treated in accordance with the AUA guideline for we retrospectively reviewed our institutional transplant the management of nonmuscle invasive bladder cancer 2 Advances in Urology (Hall MC, J Urol, 2007). BCG was used in select patients, (36–84) months. One patient with T1 high-grade BUC and and criteria for consideration of BCG included patients at a history of bilateral cutaneous ureterostomies (performed high risk for recurrence, large tumors, multifocal tumors, following transplantation for treatment of vesicoureteral fis- high-grade disease, or presence of CIS. Surgeon preference tula) underwent radical cystectomy and ureteroureterostomy also influenced the use of intravesical BCG, as multiple and remains disease-free with a followup of 98 months. None different urologists provided treatment to patients in the of the patients with T1 disease progressed to muscle invasive current series. BCG was administered as described by disease (Table 1). Lamm et al. Radical cystectomy with urinary diversion or Muscle invasive transitional cell carcinoma was diag- palliative external beam radiotherapy was used for those nosed in four patients at a median of 3.6 years (range 2 with muscle invasive disease. None of the patients with to 6 years) following transplantation (Table 2). Two patients muscle invasive disease received neoadjuvant or adjuvant underwent radical cystectomy with urinary diversion, one therapies. The radiation field was not significantly altered in with orthotopic neobladder, and one with percutaneous renal transplant patients, and immunosuppressive regimens allograft nephrostomy tube placement (due to significant remained unchanged in all patients. Patients were followed scar tissue and adhesions limiting small bowel mobilization postoperatively at regular intervals per established surveil- and creation of urinary diversion). Both patients remain lance protocols. recurrence-free at 24 and 36 months of followup, respec- tively. Ileal conduit urinary diversion and palliative radiation were performed in one patient with unresectable disease, 3. Results who subsequently died from disseminated intravascular coagulation 16 months following cancer diagnosis. One Of the 2,925 renal and 2,761 liver transplant recipients patient received palliative XRT and died of diffuse liver reviewed, we identified eight patients following kidney and pulmonary metastases 12 months following treatment. transplant and three patients following liver transplant (n = Criteria for consideration of palliative XRT include evidence 11, 0.2%) who developed bladder cancer. The mean age of metastases at the time of diagnosis of muscle invasive BUC at transplantation was 62 ± 13 years (range 38–82 years) and unresectable disease. and all were male. Bladder cancer diagnosis was made at a mean interval of 39 ± 24 months (range 3.5–76 months) following transplantation. Mean age at the time of diagnosis 4. Discussion was 65 ± 12 years (range 44–83), and mean followup was 40 ± 27 months (range 12–98 months). Maintenance The increased risk for the development of malignancies immunotherapy protocols included tacrolimus + pred- following renal and liver transplant is well documented [9]. nisone, tacrolimus + mycophenolate mofetil + prednisone, Of special interest to urologists is the increased incidence tacrolimus + mycophenolate mofetil, and tacrolimus alone of genitourinary malignancies, including kidney and bladder in 54.5%, 27.3%, 9.1%, and 9.1% of patients, respectively. cancer, following transplantation [10]. Transplant recipients It was not necessary to alter immunotherapy protocols are up to 3.3-times more likely to develop BUC than the gen- following diagnosis or in the treatment of BUC. There were eral population [4]. More alarmingly, recent data also suggest no deleterious effects on graft survival or function following that renal transplant recipients and patients with end-stage urologic intervention. Prior to urologic intervention, mean renal disease present with higher-stage [5], biologically more serum creatinine was 1.4 mg/dL (range 0.9–2.0 mg/dL). At aggressive tumors [11] and experience worse outcomes than last followup, serum electrolyte levels were normal, and the general population [11]. The etiology of increased risk for mean serum creatinine level was 1.5 ± 0.4 mg/dL (range 1.0– BUC among transplant recipients is multifactorial [5], and in 2.1 mg/dL). Liver function tests were not affected by urologic addition to common risk factors for BUC such as smoking, intervention. also includes risk factors unique to the transplant recipient, Ten patients presented with gross hematuria, and one such as direct cytotoxic damage from immunosuppressive patient was diagnosed incidentally by cross-sectional imag- agents [12], impaired DNA repair mechanisms in immuno- ing. Imaging studies performed at the time of diagnosis compromised patients [13], impaired protection against viral revealed no evidence of lymphadenopathy, metastasis, or oncogenes [14], and urinary tract infections [15]. upper tract urothelial carcinoma. Two patients with low- The incidence of de novo BUC following renal and liver grade T1 BUC were managed by transurethral resection transplantation in our series is 0.27% and 0.11%, respec- (TURBT) alone. Three patients with CIS and one patient tively, and is comparable to other series. The University with T1 BUC were treated by TURBT and adjuvant intrav- of California, San Francisco, reported the development of esical bacille Calmette-Guerin (BCG) immunotherapy. The de novo BUC in 0.08% of over 6000 renal transplant patient with T1
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